Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
relugolix
Relugolix is a nonpeptide gonadotropin-releasing hormone (GnRH) receptor antagonist that inhibits pituitary release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thereby suppressing testosterone production from the testes. The reduction in testosterone concentrations to below physiologic levels inhibits the proliferation of hormone-dependent prostate cancer cells.
| Bioavailability |
~12% |
| Effects with food |
No clinically meaningful effect on exposure when given with food. AUC and Cmax were reduced by 19% and 21%, respectively, following a high-fat, high-calorie meal. |
| Time to reach steady state |
7 days (including loading dose on day 1) |
| Peak plasma levels |
~2 hours |
Distributed widely to tissues
| PPB |
68-71%, mainly to albumin, and α1-acid glycoprotein to a lesser extent |
Relugolix is mainly metabolized by CYP3A, with a lesser contribution from CYP2C8 in vitro.
| Half-life |
25 hours (effective) 61 hours (terminal) |
| Feces |
81% (4% unchanged) |
| Urine |
4% (2% unchanged) |
- Prostate cancer
Refer to the product monograph for a full list and details of approved indications
Emetogenic Potential:
The following table lists adverse effects that occurred in patients with advanced prostate cancer treated with relugolix versus leuprolide in a single-agent phase III study. It also includes severe, life-threatening and post-marketing adverse effects from other sources.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | Arrhythmia (<1%) | E | |||
| Arterial thromboembolism (3%) | E D | ||||
| Atrioventricular block (<1%) | E | ||||
| Heart failure (<1%) | E D | ||||
| Hypertension (8%) | E | ||||
| QT interval prolonged (5%) (2% severe) | E D | ||||
| Dermatological | Hyperhidrosis (<5%) | E | |||
| Rash (<5%) (includes urticaria) | I E | ||||
| Gastrointestinal | Constipation (12%) | E | |||
| Diarrhea (12%) | E | ||||
| Nausea (6%) | E | ||||
| Weight gain (8%) | E | ||||
| General | Fatigue (26%) | E | |||
| Hematological | Anemia (<5%) | E | |||
| Hemorrhage (<1%) | E | ||||
| Hypersensitivity | Angioedema (rare) | I E | |||
| Musculoskeletal | Fracture (<1%) | D L | |||
| Musculoskeletal pain (30%) | E | ||||
| Nervous System | Depression (<5%) | E D | |||
| Dizziness (6%) | E | ||||
| Headache (6%) | E | ||||
| Insomnia (7%) | E | ||||
| Renal | Acute kidney injury (<1%) | E | |||
| Reproductive and breast disorders | Gynecomastia (<5%) | E D | |||
| ↓ Libido (<5%) | E | ||||
| Vascular | Hot flashes (54%) | E | |||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
The most common side effects for relugolix include hot flashes, musculoskeletal pain, fatigue, constipation, and diarrhea.
Refer to protocol by which the patient is being treated.
Correct potassium, calcium, and magnesium abnormalities prior to initiation.
Oral:
- Loading dose: 360 mg on day 1
- Maintenance dose: 120 mg daily, starting on day 2
Coadministration with an anti-androgen is not necessary since relugolix does not cause a testosterone surge and the associated clinical flare.
If relugolix is interrupted for > 7 days, restart treatment with a loading dose of 360 mg on day 1, followed by 120 mg daily thereafter.
Dose adjustment for drug-drug interactions:
Refer to Interactions section for dosing recommendations when co-administering with P-gp inhibitors or combined P-gp and strong CYP3A inducers.
There are no dose reductions for relugolix. Doses may be held for up to 10 days for evaluation and treatment of adverse effects, if required. (Shore et al)
If doses are held for >7 days, restart with a loading dose as outlined above.
| Hepatic Impairment | Relugolix Dose |
|
Mild |
No dose adjustment required. |
|
Moderate |
|
|
Severe |
No data available. |
| Creatinine Clearance (mL/min) | Relugolix Dose |
| ≥ 15 | No dose adjustment required. |
| < 15 Or end-stage renal disease, with or without hemodialysis |
No data available. |
No dose adjustment in patients ≥ 65 years of age is required. There were no overall differences in safety or effectiveness of relugolix when compared to younger patients. Age had no clinically relevant impact on the pharmacokinetics of relugolix or testosterone response in patients aged 45 to 91 years.
No clinically meaningful effects on relugolix exposure were observed based on race or ethnicity.
The safety and effectiveness of relugolix in patients aged < 18 years have not been established.
- Administer relugolix with or without food.
- Tablets should be swallowed whole and not crushed or chewed.
- If a dose is missed, administer the dose as soon as possible within 12 hours of missed dose. If the dose is missed by more than 12 hours, skip the dose and administer the next dose at the next planned time. Do not give extra tablets to make up for the missed dose.
- If doses are held for >7 days, restart with a loading dose as outlined in the Dosing section.
- Store between 15°C to 30°C in the original container.
- Patients who have a hypersensitivity to this drug or any of its components
-
Androgen deprivation therapy can prolong the QT interval. Consider the risks versus benefits of using relugolix in patients who have risk factors for QTc prolongation and torsade de pointes.
-
Long-term suppression of testosterone is associated with decreased bone density, which may increase the risk of osteoporosis and bone fractures.
Other Drug Properties:
-
Carcinogenicity:
No
-
Mutagenicity:
No
-
Clastogenicity:
No
-
Embryotoxicity:
Documented in animals
-
Fetotoxicity:
Documented in animals
-
Teratogenicity:
Documented in animals
-
Abortifacient effects:
Documented in animals
-
Pregnancy:
Relugolix is only indicated in patients with prostate cancer. Adequate contraception should be used by patients and their partners during treatment, and for at least 2 weeks after the last dose.
-
Excretion into breast milk:
Documented in animals
-
Breastfeeding:
Relugolix is only indicated in patients with prostate cancer. There are no data on the presence of relugolix or its metabolites in human milk, on the effects of the breastfed child or milk production.
-
Fertility effects:
Probable
Documented in studies in male animals
In vitro, relugolix is a(n):
- substrate of CYP3A and CYP2C8
- inducer of CYP3A4 and CYP2B6
- substrate of P-gp
- inhibitor of BCRP and P-gp (clinical significance not established)
No clinically meaningful differences in relugolix pharmacokinetics were observed when co-administered with voriconazole, a strong CYP3A inhibitor.
Relugolix suppresses the pituitary gonadal system, which may affect diagnostic test results of pituitary gonadotropic and gonadal functions conducted during and after treatment.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| Oral P-glycoprotein inhibitors | ↑ relugolix concentration and/or toxicity (e.g. erythromycin ↑ relugolix exposure by 3.5-fold) | Relugolix is a P-gp substrate | Avoid co-administration. If must co-administer, give relugolix first and separate dosing by at least 6 hours; monitor closely for toxicity. Or hold relugolix for up to 2 weeks if a short course of treatment with a P-gp inhibitor is required. If doses are held for >7 days, restart with a loading dose as outlined in the Dosing section. |
| Combined P-gp and strong CYP3A inducers (i.e. rifampin) | ↓ relugolix concentration and/or efficacy (e.g. rifampin ↓ relugolix exposure by 55%) | Relugolix is a P-gp and CYP3A substrate | Avoid co-administration. If must co-administer, ↑ relugolix dose to 240 mg daily. Resume the 120 mg daily dose after discontinuation of the combined P-gp and strong CYP3A inducer. |
| Medications that may prolong QT (i.e. amiodarone, procainamide, sotalol, venlafaxine, amitriptyline, sunitinib, methadone, chloroquine, clarithromycin, haloperidol, fluconazole, moxifloxacin, domperidone, ondansetron) | ↑ risk of QT prolongation | Additive effects | Avoid co-administration. |
| Medications that can affect electrolyte levels (i.e. thiazide and related diuretics, laxatives and enemas, amphotericin B, high-dose corticosteroids, and proton pump inhibitors) | ↑ risk of QT prolongation | Electrolyte disturbances can ↑ risk of QT prolongation | Caution with concomitant use. |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
| Monitor Type | Monitor Frequency |
|---|---|
CBC |
Baseline and as clinically indicated |
Liver function tests |
Baseline and as clinically indicated |
Renal function tests |
Baseline and as clinically indicated |
ECG and serum electrolyte levels (potassium, calcium, and magnesium) |
Baseline, at each visit, and as clinically indicated (more frequently in patients with electrolyte abnormality or at risk of QT prolongation) |
Prostate specific antigen (PSA) |
Baseline and as clinically indicated |
Testosterone serum concentration |
Baseline and as clinically indicated if PSA increases |
Clinical toxicity assessment for hot flashes, musculoskeletal pain, fatigue, GI effects, fractures/ osteoporosis |
Baseline and as clinically indicated |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
NCI drug dictionary: relugolix. Accessed February 28, 2025.
Prescribing Information: Orgovyx® (relugolix). Sumitomo Pharma America, Inc. October 2024
Product Information: Orgovyx® (relugolix). Accord Healthcare. November 2024.
Product Monograph: Orgovyx® (relugolix). Sumitomo Pharma Canada, Inc. September 2024.
Shore ND, Saad F, Cookson MS, et al. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187-2196.
April 2025 New drug monograph
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.